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Purpose Pre-operative scores based on patient characteristics are commonly used to predict hip fracture outcomes. Mobility, an indicator of pre-operative function, has been neglected as a potential predictor. We assessed the ability of pre-fracture mobility to predict post-operative outcomes following hip fracture. Methods We analysed prospectively collected data from hip fracture surgery patients at a large-volume trauma unit. Mobility was classified into four groups. Post-operative outcomes studied were mortality and residence at 30 days, medical complications within 30- or 60-days post-operatively, and prolonged length of stay (LOS, ≥ 28 days). We performed multivariate regression analyses adjusting for age and sex to assess the discriminative ability of the Nottingham Hip Fracture Score (NHFS), with and without mobility, for predicting outcomes using the area under the receiver operating characteristic curve (AUROC). Results 1919 patients were included, mean age 82.6 (SD 8.2); 1357 (70.7%) were women. Multivariate analysis demonstrated patients with worse mobility had a 1.7–5.5-fold higher 30-day mortality (p ≤ 0.001), and 1.9–3.2-fold higher likelihood of prolonged LOS (p ≤ 0.001). Worse mobility was associated with a 2.3–3.8-fold higher likelihood of living in a care home at 30-days post-operatively (p p ≤ 0.001). Addition of mobility improved NHFS discrimination for discharge location, AUROC NHFS 0.755 [0.733–0.777] to NHFS + mobility 0.808 [0.789–0.828], and LOS, AUROC NHFS 0.584 [0.557–0.611] to NHFS + mobility 0.616 [0.590–0.643]. Conclusion Incorporating mobility assessment into risk scores may improve casemix adjustment, prognostication following hip fracture, and identify high-risk patient groups requiring enhanced post-operative care at admission.

Numerous approaches are used to characterise multiple long-term conditions (MLTC), including counts and indices. Few studies have compared approaches within the same dataset. We aimed to characterise MLTC using simple approaches, and compare their prevalence estimates of MLTC and associations with emergency hospital admission in the UK Biobank.We used baseline data from 495,465 participants (age 38-73 years) to characterise MLTC using four approaches: Charlson index (CI), Byles index (BI), count of 43 conditions (CC) and count of body systems affected (BC). We defined MLTC as more than two conditions using CI, BI and CC, and more than two body systems using BC. We categorised scores (incorporating weightings for the indices) from each approach as 0, 1, 2 and 3+. We used linked hospital episode statistics and performed survival analyses to test associations with an endpoint of emergency hospital admission or death over 5 years.The prevalence of MLTC was 44% (BC), 33% (CC), 6% (BI) and 2% (CI). Higher scores using all approaches were associated with greater outcome rates independent of sex and age group. For example, using CC, compared with score 0, score 2 had 1.95 (95% CI: 1.91, 1.99) and a score of 3+ had 3.12 (95% CI: 3.06, 3.18) times greater outcome rates. The discriminant value of all approaches was modest (C-statistics 0.60-0.63).The counts classified a greater proportion as having MLTC than the indices, highlighting that prevalence estimates of MLTC vary depending on the approach. All approaches had strong statistical associations with emergency hospital admission but a modest ability to identify individuals at risk.

Data sharing statement: The protocol, consent form, definition and derivation of clinical characteristics and outcomes, training materials, regulatory documents, information about requests for data access, and other relevant study materials are available online at https://www.phosp.org/ Copyright © 2023 The Author(s). Background: The scale of COVID-19 and its well documented long-term sequelae support a need to understand long-term outcomes including frailty. Methods: This prospective cohort study recruited adults who had survived hospitalisation with clinically diagnosed COVID-19 across 35 sites in the UK (PHOSP-COVID). The burden of frailty was objectively measured using Fried's Frailty Phenotype (FFP). The primary outcome was the prevalence of each FFP group—robust (no FFP criteria), pre-frail (one or two FFP criteria) and frail (three or more FFP criteria)—at 5 months and 1 year after discharge from hospital. For inclusion in the primary analysis, participants required complete outcome data for three of the five FFP criteria. Longitudinal changes across frailty domains are reported at 5 months and 1 year post-hospitalisation, along with risk factors for frailty status. Patient-perceived recovery and health-related quality of life (HRQoL) were retrospectively rated for pre-COVID-19 and prospectively rated at the 5 month and 1 year visits. This study is registered with ISRCTN, number ISRCTN10980107. Findings: Between March 5, 2020, and March 31, 2021, 2419 participants were enrolled with FFP data. Mean age was 57.9 (SD 12.6) years, 933 (38.6%) were female, and 429 (17.7%) had received invasive mechanical ventilation. 1785 had measures at both timepoints, of which 240 (13.4%), 1138 (63.8%) and 407 (22.8%) were frail, pre-frail and robust, respectively, at 5 months compared with 123 (6.9%), 1046 (58.6%) and 616 (34.5%) at 1 year. Factors associated with pre-frailty or frailty were invasive mechanical ventilation, older age, female sex, and greater social deprivation. Frail participants had a larger reduction in HRQoL compared with before their COVID-19 illness and were less likely to describe themselves as recovered. Interpretation: Physical frailty and pre-frailty are common following hospitalisation with COVID-19. Improvement in frailty was seen between 5 and 12 months although two-thirds of the population remained pre-frail or frail. This suggests comprehensive assessment and interventions targeting pre-frailty and frailty beyond the initial illness are required. Funding: UK Research and Innovation and National Institute for Health Research. The study was funded with grants from UK Research and Innovation (MR/V027859/1) and The National Institute of Health Research (COV0319). This study would not be possible without all the participants who have given their time and support. We thank all the participants and their families. We thank the many research administrators, health-care and social-care professionals who contributed to setting up and delivering the study at all of the 40 NHS trusts and 25 research institutions across the UK, as well as all the supporting staff at the NIHR Clinical Research Network, Health Research Authority, Research Ethics Committee, Department of Health and Social Care, Public Health Scotland, and Public Health England, and support from the ISARIC Coronavirus Clinical Characterisation Consortium. The authors would also like to acknowledge the support of the eDRIS Team (Public Health Scotland) for their involvement in obtaining approvals, provisioning and linking data and the use of the secure analytical platform within the National Safe Haven.

Background: Trials of hospital deprescribing interventions have demonstrated limited changes in practitioner behaviour. Our previous research characterised four barriers and one enabler to geriatricians and pharmacists deprescribing in hospital that require addressing by a behaviour change intervention. Six behaviour change techniques (BCTs) have also been selected by the target audience using the hospital Deprescribing Implementation Framework (hDIF). This research aimed to co-design and operationalise the content, mode of delivery and duration/intensity of the six selected BCTs to develop the CompreHensive geriAtRician-led MEdication Review (CHARMER) deprescribing intervention. Methods: We established co-design panels at three hospitals representing contextual factors likely to influence CHARMER implementation. Panels comprised geriatricians, pharmacists and other hospital staff likely to be involved in implementation. We convened two rounds of co-design workshops with each hospital to design a prototype for each BCT, which went for feedback at a final workshop attended by all three hospital panels. Results: The six BCTs were co-designed into an intervention comprising:(1&2) Pharmacists' workshop with pros and cons of deprescribing activities, and videos of salient patient cases3 Regular geriatrician and pharmacist deprescribing briefings4 Videos of geriatricians navigating challenging deprescribing consultations5 Hospital deprescribing action plan6 Dashboard to benchmark deprescribing activitiesAutomated prompts to flag high-risk patients for deprescribing and a primary and secondary care deprescribing forum were proposed as additional BCTs by stakeholders. These were later excluded as they were not fidelitous to the theoretical determinants of geriatricians' and pharmacists’ deprescribing behaviours. Conclusions: This study illustrates the integration of theory and co-design methodology with the target audience and staff likely to be involved in implementation of a hospital deprescribing behaviour change intervention. The development of an intervention that remains faithful to the underpinning mechanisms of action of behaviour change is a strength of this approach. publishedVersion

Remotely collected physical performance measures could improve inclusion of under-served groups in clinical research as well as enabling continuation of research in pandemic conditions. It is unclear whether remote collection is feasible and acceptable to older patients, or whether results are comparable to face-to-face measures. We conducted a systematic review according to a prespecified protocol. We included studies with mean participant age ≥ 60 years, with no language restriction. Studies examining the gait speed, Short Physical Performance Battery, distance walk tests, grip strength, Tinetti score, Berg balance test, sit-to-stand test and timed up and go were included. Reports of feasibility, acceptability, correlation between remote and face-to-face assessments and absolute differences between remote and face-to-face assessments were sought. Data were synthesised using Synthesis Without Meta-analysis methodology; 30 analyses from 17 publications were included. Study size ranged from 10 to 300 participants, with a mean age ranging from 61 to >80 years. Studies included a broad range of participants and conditions. Most studies had a moderate or high risk of bias. Only two studies undertook assessment of acceptability or feasibility, reporting good results. Correlation between face-to-face and remote measures was variable across studies, with no measure showing consistently good correlation. Only nine studies examined the accuracy of remote measures; in six studies, accuracy was rated as good (

Premature cardiovascular disease and death with a functioning graft are leading causes of death and graft loss, respectively, in kidney transplant recipients (KTRs). Vascular stiffness and calcification are markers of cardiovascular disease that are prevalent in KTR and associated with subclinical vitamin K deficiency. We performed a single-center, phase II, parallel-group, randomized, double-blind, placebo-controlled trial (ISRCTN22012044) to test whether vitamin K supplementation reduced vascular stiffness (MRI-based aortic distensibility) or calcification (coronary artery calcium score on computed tomography) in KTR over 1 year of treatment. The primary outcome was between-group difference in vascular stiffness (ascending aortic distensibility). KTRs were recruited between September 2017 and June 2018, and randomized 1:1 to vitamin K (menadiol diphosphate 5 mg; n = 45) or placebo (n = 45) thrice weekly. Baseline demographics, clinical history, and immunosuppression regimens were similar between groups. There was no impact of vitamin K on vascular stiffness (treatment effect -0.23 [95% CI -0.75 to 0.29] × 10-3 mmHg-1 ; p = .377), vascular calcification (treatment effect -141 [95% CI - 320 to 38] units; p = .124), nor any other outcome measure. In this heterogeneous cohort of prevalent KTR, vitamin K supplementation did not reduce vascular stiffness or calcification over 1 year. Improving vascular health in KTR is likely to require a multifaceted approach.

Background Half of older people are prescribed unnecessary/inappropriate medications that are not routinely deprescribed in hospital hence there is a need for deprescribing trials. We aimed to develop a Core Outcome Set (COS) for deprescribing trials for older people under the care of a geriatrician during hospital admission. Methods We developed a list of potentially relevant outcomes from the literature. Using a two-round Delphi survey of stakeholder groups representing older people and carers, hospital clinicians, hospital managers, and ageing/deprescribing researchers, each outcome was scored according to Grading of Recommendations Assessment, Development and Evaluation, followed by two consensus workshops to finalise the COS. Results Two hundred people completed Round 1 and 114 completed Round 2. Representing all stakeholder groups, 10 people participated in workshop 1 and 10 in workshop 2. Six outcomes were identified as most important, feasible and acceptable to collect in a trial: number of prescribed medicines stopped; number of prescribed medicines with dosage reduced; quality of life; mortality; adverse drug events and number of hospital stays. Three other outcomes were identified as important, but currently too burdensome to collect: number of potentially inappropriate medicines prescribed; burden from medication routine; and medication-related admissions to hospital. Conclusions A COS represents the minimum outcomes that should be collected and reported. Whilst uncommon practice for COS development, the value of considering outcome collection feasibility is demonstrated by the removal of three potential outcomes that, if included, may have compromised COS uptake due to challenges with collecting the data.

Randomised trials, especially those intended to directly inform clinical practice and policy, should be designed to reflect all those who could benefit from the intervention under test should it prove effective. This does not always happen. The UK National Institute for Health and Care Research (NIHR) INCLUDE project identified many groups in the UK that are under-served by trials, including ethnic minorities.This guidance document presents four key recommendations for designing and running trials that include the ethnic groups needed by the trial. These are (1) ensure eligibility criteria and recruitment pathway do not limit participation in ways you do not intend, (2) ensure your trial materials are developed with inclusion in mind, (3) ensure staff are culturally competent and (4) build trusting partnerships with community organisations that work with ethnic minority groups. Each recommendation comes with best practice advice, public contributor testimonials, examples of the inclusion problem tackled by the recommendation, or strategies to mitigate the problem, as well as a collection of resources to support implementation of the recommendations.We encourage trial teams to follow the recommendations and, where possible, evaluate the strategies they use to implement them. Finally, while our primary audience is those designing, running and reporting trials, we hope funders, grant reviewers and approvals agencies may also find our guidance useful.

Background A postural blood pressure assessment is required to diagnose Orthostatic Hypotension. With increasing remote consultations, alternative methods of performing postural blood pressure assessment are required. Objective Determine whether postural blood pressure measurement at home, without a clinician, is reliable, feasible and safe. Design Service improvement project within a falls and syncope service in Northeast England. Subjects Eligibility criteria: aged ≥60 years; postural blood pressure measurement is indicated and is physically and cognitively able to perform. Exclusion criteria: nursing home residents, attending clinic in person. Methods Postural blood pressure measurements were performed in patients’ homes under clinical observation. Patient-led assessments were performed independent of the clinician, following written guidance. This was followed by a clinical-led assessment after 10-minute supine rest. Outcomes Agreement between patient and clinician derived postural blood pressure values and diagnosis of Orthostatic Hypotension; intervention safety, feasibility and acceptability. Results Twenty-eight patients were eligible and 25 participated (mean age 75, median Clinical Frailty Score five). There was 95% agreement (Cohen’s kappa 0.90 (0.70, 1.00)) between patient and clinician derived readings to diagnose orthostatic hypotension. Postural systolic blood pressure drop correlated strongly (r = 0.80), with patient derived readings overestimating by 1 (−6, 3) mmHg. Limits of agreement, determined via Bland Altman analysis, were +17 and −20 mmHg, greater than pre-determined maximum clinically important difference (±5 mmHg). Twenty participants performed valid postural blood pressure assessments without clinical assistance. Conclusions Patient-led postural blood pressure assessment at home is a reliable, safe and acceptable method for diagnosing Orthostatic Hypotension.

Objectives: risk stratification scores are used in hip fracture surgery, but none incorporate objective tests for low muscle strength. Grip strength testing is simple and cheap but not routinely assessed for patients with hip fracture. This project aimed to assess the feasibility of implementing grip strength testing into admission assessment of patients with hip fracture. Methods: a scalable protocol and a corresponding training programme of instructional presentations and practical assessments were designed and delivered by and for physiotherapy staff. Grip strength values were collected pre-surgery on patients with hip fracture at a single centre whilst supine in bed. Implementation of the process was evaluated using narrative, quantitative and cost measures. Results: 53 hip fracture patients with a mean age 80.6 (SD 10.4), of which 36 (67.9%) were female, were included. Testing was offered to 42/52 (81%) patients. Cognitive impairment prevented 14/42 (33%) of patients from completing testing; one patient declined testing. Of the 27 patients who completed testing, 14/27 (52%) had low grip strength as defined by EWGSOP2 criteria. The projected cost of testing for one year was £2.68-£2.82 per patient. Fidelity to the protocol was high using multiple criteria. Conclusions: grip strength assessment is acceptable to physiotherapy staff and can be rapidly and cost-effectively implemented into hip fracture admission assessment.

Purpose of review \ud Vascular calcification is a common and important cardiovascular risk factor in patients with chronic kidney disease (CKD). Recent advances in the understanding of the biology of vascular calcification implicate vitamin K-dependent proteins as important regulators in this process. This review highlights recent key advances in vascular biology, epidemiology, and clinical trials in this rapidly evolving field.\ud \ud Recent findings \ud Vitamin K deficiency is associated with increasing severity of vascular calcification among patients with CKD, but the relationship with cardiovascular disease and mortality is inconsistent. Vitamin K may reduce calcification propensity by improving the activity of vitamin K-dependent calcification inhibitors or by down-regulating components of the innate immune system to reduce inflammation. However, recent randomized controlled trials in patients with diabetes, CKD, renal transplant, and on hemodialysis have failed to demonstrate improvement in vascular calcification or stiffness after vitamin K treatment.\ud \ud Summary \ud Current evidence does not support a clinically useful role for vitamin K supplementation to prevent or reverse vascular calcification in patients with CKD. Knowledge gaps remain, particularly whether higher doses of vitamin K, longer duration of supplementations, or use a vitamin K as a part of a package of measures to counteract vascular calcification might be effective.

Background Awareness of sarcopenia and frailty is growing and both are known to be potentially reversible with effective resistance training. We aimed to establish whether existing exercise programmes offered to people with sarcopenia or frailty adhere to the known evidence base. Methods We conducted a national on-line survey of practitioners delivering exercise programmes to older people with sarcopenia or frailty. The link to the online survey was distributed through the British Geriatrics Society, Chartered Society of Physiotherapy Special Interest Group for Older People (AGILE), the NHS England Future Collaboration Platform “Supporting People Living with Frailty” forum and social media. Questions covered target population and aims of the exercise programme, type, duration and frequency of exercise, progress assessment and outcome measures. Descriptive analyses were conducted using SPSS v24. Results 136 responses were received from respondents who worked for NHS Trusts, clinical commissioning groups, private practices, and third sector providers. 94% of respondents reported prescribing or delivering exercise programmes to people with sarcopenia or frailty. Most programmes (81/135 [60%]) were primarily designed to prevent or reduce falls. Resistance training was reported as the main focus of the programme in only 11/123 (9%); balance training was the main focus in 61/123 (50%) and functional exercise in 28/123 (23%). Exercise was offered once a week or less by 81/124 (65%) of respondents; the median number of sessions offered was 8.5 (IQR 6 to 12). Outcome measures suitable for assessing the effect of resistance training programmes were reported by fewer than half of respondents (hand grip: 13/119 [11%]; chair stands: 55/119 [46%], short physical performance battery: 4/119 [3%]). Conclusions Current exercise programmes offered to older people with sarcopenia or frailty lack the frequency, duration or specificity of exercise likely to improve outcomes for this group of patients.

Background Impaired physical performance is common in older people with advanced chronic kidney disease. It is unclear which metabolic derangements contribute to this impairment. This analysis examined cross-sectional associations between renal biochemical indices and physical performance in older people with advanced chronic kidney disease. Methods We analysed data from the BiCARB multicentre trial, which enrolled patients aged 60 and over, with chronic kidney disease stage 4 or 5, not on dialysis, and with serum bicarbonate Results The analysis included 300 participants (mean age 74 years; 86 [29%] women). Mean baseline SPPB was 8.1 points (SD 2.3); mean six-minute walk distance was 311 m (SD 132). Age (r = −0.27, p Conclusions Some biochemical markers related to kidney function are modestly associated with physical performance in older people with advanced chronic kidney disease; patterns differ between different performance measures.

Background Mitochondrial dysfunction has been proposed as a therapeutic target to improve muscle strength and endurance, but the contribution that mitochondrial dysfunction makes to impaired skeletal muscle performance in older people remains unclear. We studied the relationship between phosphocreatine recovery rate (a measure of skeletal muscle mitochondrial function) and physical performance in older people. Methods We analysed data from the Allopurinol in Functional Impairment (ALFIE) trial. Participants aged 65 and over, who were unable to walk 400 m in six minutes, underwent 31P magnetic resonance spectroscopy of the calf after exercise at baseline and at 20 weeks follow up. The phosphocreatine recovery half-life time (t-half) was derived as a measure of mitochondrial function. Participants also undertook the 6-minute walk distance, the Short Physical Performance Battery test (SPPB), and had muscle mass measured using bio-impedance analysis. Bivariate correlations and multivariable regression analyses were conducted to determine associations between t-half and baseline factors. Results One hundred and seventeen people underwent baseline 31P magnetic resonance spectroscopy, mean age 80.4 years (SD 6.0); 56 (48%) were female. Mean 6-minute walk was 291 m (SD 80) and mean SPPB score was 8.4 (SD 1.9). T-half was significantly correlated with SPPB score (r = 0.22, p = 0.02) but not with 6-minute walk distance (r = 0.10, p = 0.29). In multivariable linear regression, muscle mass and weight, but not t-half, were independently associated with SPPB score and with 6-minute walk distance. The change in t-half between baseline and 20 weeks was not significantly associated with the change in SPPB (r = 0.03, p = 0.79) or with the change in 6-minute walk distance (r = −0.11, p = 0.28). Conclusion Muscle mass, but not phosphocreatine recovery time, was associated with Short Physical Performance Battery score and 6-minute walk distance in this cohort of older people with functional impairment.

BackgroundAs the populations of lower-income and middle-income countries age, multimorbidity is increasing, but there is little information on its long-term consequences. We aimed to show associations between multimorbidity and outcomes of mortality and hospitalisation in Iran, a middle-income country undergoing rapid economic transition.MethodsWe conducted a secondary analysis of longitudinal data collected in the Golestan Cohort Study. Data on demographics, morbidities and lifestyle factors were collected at baseline, and information on hospitalisations or deaths was captured annually. Logistic regression was used to analyse the association between baseline multimorbidity and 10-year mortality, Cox-proportional hazard models to measure lifetime risk of mortality and zero-inflation models to investigate the association between hospitalisation and multimorbidity. Multimorbidity was classified as ≥2 conditions or number of conditions. Demographic, lifestyle and socioeconomic variables were included as covariables.ResultsThe study recruited 50 045 participants aged 40–75 years between 2004 and 2008, 47 883 were available for analysis, 416 (57.3%) were female and 12 736 (27.94%) were multimorbid. The odds of dying at 10 years for multimorbidity defined as ≥2 conditions was 1.99 (95% CI 1.86 to 2.12, pConclusionThe long-terms effects of multimorbidity on mortality and hospitalisation are similar in this population to those seen in high-income countries.

Background A failure of clinical trials to retain participants can influence the trial findings and significantly impact the potential of the trial to influence clinical practice. Retention of participants involves people, often the trial participants themselves, performing a behaviour (e.g. returning a questionnaire or attending a follow-up clinic as part of the research). Most existing interventions that aim to improve the retention of trial participants fail to describe any theoretical basis for the potential effect (on behaviour) and also whether there was any patient and/or participant input during development. The aim of this study was to address these two problems by developing theory- informed, participant-centred, interventions to improve trial retention. Methods This study was informed by the Theoretical Domains Framework and Behaviour Change Techniques Taxonomy to match participant reported determinants of trial retention to theoretically informed behaviour change strategies. The prototype interventions were described and developed in a co-design workshop with trial participants. Acceptability and feasibility (guided by (by the Theoretical Framework of Acceptability) of two prioritised retention interventions was explored during a focus group involving a range of trial stakeholders (e.g. trial participants, trial managers, research nurses, trialists, research ethics committee members). Following focus group discussions stakeholders completed an intervention acceptability questionnaire. Results Eight trial participants contributed to the co-design of the retention interventions. Four behaviour change interventions were designed: (1) incentives and rewards for follow-up clinic attendance, (2) goal setting for improving questionnaire return, (3) participant self-monitoring to improve questionnaire return and/or clinic attendance, and (4) motivational information to improve questionnaire return and clinic attendance. Eighteen trial stakeholders discussed the two prioritised interventions. The motivational information intervention was deemed acceptable and considered straightforward to implement whilst the goal setting intervention was viewed as less clear and less acceptable. Conclusions This is the first study to develop interventions to improve trial retention that are based on the accounts of trial participants and also conceptualised and developed as behaviour change interventions (to encourage attendance at trial research visit or return a trial questionnaire). Further testing of these interventions is required to assess effectiveness.

Non-communicable diseases are increasing in developing countries and control of diabetes and hypertension is needed to reduce rates of the leading causes of morbidity and mortality, stroke and ischaemic heart disease. We evaluated a programme in Cambodia, financed by a revolving drug fund, which utilizes Peer Educators to manage diabetes and hypertension in the community. We assessed clinical outcomes and retention in the programme. For all people enrolled in the programme between 2007 and 2016, the average change in blood pressure (BP) and percentage with controlled hypertension (BP < 140/

Introduction Increased left ventricular mass index (LVMI) is associated with mortality in end-stage renal disease. LVMI regression may improve outcomes. Allopurinol has reduced LVMI in randomized controlled trials in chronic kidney disease, diabetes, and ischemic heart disease. This study investigated whether allopurinol would regress LVMI in hemodialysis patients. Methods This was a randomized placebo-controlled double-blind multicenter trial funded by the British Heart Foundation (PG/12/72/29743). A total of 80 patients undergoing regular maintenance hemodialysis were recruited from NHS Tayside, NHS Greater Glasgow and Clyde and NHS Ayrshire and Arran in Scotland, UK. Participants were randomly assigned on a 1:1 ratio to 12 months of therapy with allopurinol 300 mg or placebo after each dialysis session. The primary outcome was change in LVMI, as assessed by cardiac magnetic resonance imaging (CMRI) at baseline and 12 months. Secondary outcomes were change in BP, flow-mediated dilation (FMD), augmentation indices (AIx), and pulse wave velocity (PWV). Results A total of 53 patients, with a mean age of 58 years, completed the study and had CMRI follow-up data for analysis. Allopurinol did not regress LVMI (change in LVMI: placebo +3.6 ± 10.4 g/m2; allopurinol: +1.6 ± 11 g/m2; P = 0.49). Allopurinol had no demonstrable effect on BP, FMD, AIx, or PWV. Conclusion Compared with placebo, treatment with allopurinol did not regress LVMI in this trial., Graphical abstract

Older people are disproportionately affected by the COVID-19 pandemic, which has had a profound impact on research as well as clinical service delivery. This commentary identifies key challenges and opportunities in continuing to conduct research with and for older people, both during and after the current pandemic. It shares opinions from responders to an international survey, a range of academic authors and opinions from specialist societies. Priorities in COVID-19 research include its specific presentation in older people, consequences for physical, cognitive and psychological health, treatments and vaccines, rehabilitation, supporting care homes more effectively, the impact of social distancing, lockdown policies and system reconfiguration to provide best health and social care for older people. COVID-19 research needs to be inclusive, particularly involving older people living with frailty, cognitive impairment or multimorbidity, and those living in care homes. Non-COVID-19 related research for older people remains of critical importance and must not be neglected in the rush to study the pandemic. Profound changes are required in the way that we design and deliver research for older people in a world where movement and face-to-face contact are restricted, but we also highlight new opportunities such as the ability to collaborate more widely and to design and deliver research efficiently at scale and speed.

BACKGROUND: Vascular calcification, a risk factor for cardiovascular disease, is common among patients with CKD and is an independent contributor to increased vascular stiffness and vascular risk in this patient group. Vitamin K is a cofactor for proteins involved in prevention of vascular calcification. Whether or not vitamin K supplementation could improve arterial stiffness in patients with CKD is unknown. METHODS: To determine if vitamin K supplementation might improve arterial stiffness in patients in CKD, we conducted a parallel-group, double-blind, randomized trial in participants aged 18 or older with CKD stage 3b or 4 (eGFR 15–45 ml/min per 1.73 m(2)). We randomly assigned participants to receive 400 μg oral vitamin K2 or matching placebo once daily for a year. The primary outcome was the adjusted between-group difference in carotid-femoral pulse wave velocity at 12 months. Secondary outcomes included augmentation index, abdominal aortic calcification, BP, physical function, and blood markers of mineral metabolism and vascular health. We also updated a recently published meta-analysis of trials to include the findings of this study. RESULTS: We included 159 randomized participants in the modified intention-to-treat analysis, with 80 allocated to receive vitamin K and 79 to receive placebo. Mean age was 66 years, 62 (39%) were female, and 87 (55%) had CKD stage 4. We found no differences in pulse wave velocity at 12 months, augmentation index at 12 months, BP, B-type natriuretic peptide, or physical function. The updated meta-analysis showed no effect of vitamin K supplementation on vascular stiffness or vascular calcification measures. CONCLUSIONS: Vitamin K2 supplementation did not improve vascular stiffness or other measures of vascular health in this trial involving individuals with CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Vitamin K therapy to improve vascular health in patients with chronic kidney disease, ISRCTN21444964 (www.isrctn.com)

Background Improving recognition of patients at increased risk of acute kidney injury (AKI) in the community may facilitate earlier detection and implementation of proactive prevention measures that mitigate the impact of AKI. The aim of this study was to develop and externally validate a practical risk score to predict the risk of AKI in either hospital or community settings using routinely collected data. Methods Routinely collected linked datasets from Tayside, Scotland, were used to develop the risk score and datasets from Kent in the UK and Alberta in Canada were used to externally validate it. AKI was defined using the Kidney Disease: Improving Global Outcomes serum creatinine–based criteria. Multivariable logistic regression analysis was performed with occurrence of AKI within 1 year as the dependent variable. Model performance was determined by assessing discrimination (C-statistic) and calibration. Results The risk score was developed in 273 450 patients from the Tayside region of Scotland and externally validated into two populations: 218 091 individuals from Kent, UK and 1 173 607 individuals from Alberta, Canada. Four variables were independent predictors for AKI by logistic regression: older age, lower baseline estimated glomerular filtration rate, diabetes and heart failure. A risk score including these four variables had good predictive performance, with a C-statistic of 0.80 [95% confidence interval (CI) 0.80–0.81] in the development cohort and 0.71 (95% CI 0.70–0.72) in the Kent, UK external validation cohort and 0.76 (95% CI 0.75–0.76) in the Canadian validation cohort. Conclusion We have devised and externally validated a simple risk score from routinely collected data that can aid both primary and secondary care physicians in identifying patients at high risk of AKI., Graphical Abstract Graphical Abstract

Skeletal muscle aging manifests as a decline in muscle quantity and quality that accelerates with aging, increasing the risk of sarcopenia. Sarcopenia is characterized by a loss of muscle strength and mass, and contributes to adverse health outcomes in older adults. Intervention studies have shown that sarcopenia may be treated by higher protein intake in combination with resistance exercise (RE). In comparison, less is known about the role of whole protein-containing foods in preventing or treating sarcopenia. Liquid milk contains multiple nutrients and bioactive components that may be beneficial for muscle, including proteins for muscle anabolism that, alone or with RE, may have myoprotective properties. However, there is a lack of evidence about the role of milk and its effects on muscle aging. This narrative review considers evidence from three observational and eight intervention studies that used milk or fortified milk, with or without exercise, as an intervention to promote muscle health and function in older adults (aged 50-99 years). The observational studies showed no association between higher habitual milk consumption and muscle-related outcomes. The results of intervention studies using fortified milk in relation to elements of sarcopenia were also negative, with further inconclusive results from the studies using a combination of (fortified) milk and exercise. Although milk contains nutrients that may be myoprotective, current evidence does not show beneficial effects of milk on muscle health in older adults. This could be due to high habitual protein intakes (>1.0 g/kg BW/d) in study participants, differences in the type of milk (low-fat vs whole) and timing of milk consumption, length of interventions, as well as differences in the sarcopenia status of participants in trials. Adequately powered intervention studies of individuals likely to benefit are needed to test the effectiveness of a whole food approach, including milk, for healthy muscle aging.

Background Allopurinol has vascular antioxidant effects and participates in purinergic signalling within muscle. We tested whether allopurinol could improve skeletal muscle energetics and physical function in older people with impaired physical performance. Methods We conducted a randomised, double blind, parallel group, placebo-controlled trial, comparing 20 weeks of allopurinol 600 mg once daily versus placebo. We recruited community-dwelling participants aged 65 and over with baseline 6-min walk distance of Results In total, 124 participants were randomised, mean age 80 (SD 6) years. A total of 59 (48%) were female, baseline 6-min walk distance was 293 m (SD 80 m) and baseline SPPB was 8.5 (SD 2.0). Allopurinol did not significantly improve PCr recovery rate (treatment effect 0.10 units [95% CI, −0.07 to 0.27], P = 0.25). No significant changes were seen in endothelial function, quality of life, lean body mass or SPPB. Allopurinol improved 6-min walk distance (treatment effect 25 m [95% 4–46, P = 0.02]). This was more pronounced in those with high baseline oxidative stress and urate. Conclusion Allopurinol improved 6-min walk distance but not PCr recovery rate in older people with impaired physical function. Antioxidant strategies to improve muscle function for older people may need to be targeted at subgroups with high baseline oxidative stress.